The Role of the Ceramide Acyl Chain Length in Neurodegeneration: Involvement of Ceramide Synthases

Ceramide forms the backbone of all complex sphingolipids and has been the focus of considerable attention in the past few years due to the discovery that ceramide plays vital roles as an intracellular messenger. Ceramide, which consists of a sphingoid long chain base to which a fatty acid is N -acyl...

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Published in	Neuromolecular medicine Vol. 12; no. 4; pp. 341 - 350
Main Authors	Ben-David, Oshrit, Futerman, Anthony H.
Format	Journal Article
Language	English
Published	New York Humana Press Inc 01.12.2010 Springer Nature B.V
Subjects	Aging - metabolism Animals Biomedical and Life Sciences Biomedicine Brain - enzymology Brain Diseases - enzymology Ceramides - biosynthesis Ceramides - chemistry HIV Infections - enzymology Human immunodeficiency virus Humans Internal Medicine Mice Nerve Degeneration - enzymology Neurodegenerative Diseases - enzymology Neurology Neurosciences Review Paper Sphingosine N-Acyltransferase - genetics Sphingosine N-Acyltransferase - metabolism Axons Neurodegeneration Fatty acid Ceramide Sphingolipids Ceramide synthase Acyl chain
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ISSN	1535-1084 1559-1174 1559-1174
DOI	10.1007/s12017-010-8114-x

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Abstract	Ceramide forms the backbone of all complex sphingolipids and has been the focus of considerable attention in the past few years due to the discovery that ceramide plays vital roles as an intracellular messenger. Ceramide, which consists of a sphingoid long chain base to which a fatty acid is N -acylated, is synthesized in mammals by a family of ceramide synthases (CerS), each of which uses a restricted subset of fatty acyl CoAs for N -acylation. Sphingolipids are found at high levels in nervous tissue, where they perform a variety of important functions in both the adult and the maturing brain. We now review what is known about the role of the acyl chain composition of ceramides and sphingolipids in normal brain development and in neurological diseases. Specifically, we attempt to integrate the information that is available about CerS expression and activity in the brain with the changes in the acyl chain composition of ceramide and complex sphingolipids in a number of neurodegenerative diseases and conditions, such as metachromatic leukodystrophy, neuronal ceroid lipofuscinoses, HIV infection, aging, Alzheimer’s disease, ischemia, and epilepsy. We conclude that understanding the direct relationship between the CerS proteins and neurological conditions will be of great importance for delineating the precise roles of sphingolipids in the brain and is likely to be the subject of intense research activity in the years ahead.
AbstractList	Ceramide forms the backbone of all complex sphingolipids and has been the focus of considerable attention in the past few years due to the discovery that ceramide plays vital roles as an intracellular messenger. Ceramide, which consists of a sphingoid long chain base to which a fatty acid is N-acylated, is synthesized in mammals by a family of ceramide synthases (CerS), each of which uses a restricted subset of fatty acyl CoAs for N-acylation. Sphingolipids are found at high levels in nervous tissue, where they perform a variety of important functions in both the adult and the maturing brain. We now review what is known about the role of the acyl chain composition of ceramides and sphingolipids in normal brain development and in neurological diseases. Specifically, we attempt to integrate the information that is available about CerS expression and activity in the brain with the changes in the acyl chain composition of ceramide and complex sphingolipids in a number of neurodegenerative diseases and conditions, such as metachromatic leukodystrophy, neuronal ceroid lipofuscinoses, HIV infection, aging, Alzheimer's disease, ischemia, and epilepsy. We conclude that understanding the direct relationship between the CerS proteins and neurological conditions will be of great importance for delineating the precise roles of sphingolipids in the brain and is likely to be the subject of intense research activity in the years ahead.Ceramide forms the backbone of all complex sphingolipids and has been the focus of considerable attention in the past few years due to the discovery that ceramide plays vital roles as an intracellular messenger. Ceramide, which consists of a sphingoid long chain base to which a fatty acid is N-acylated, is synthesized in mammals by a family of ceramide synthases (CerS), each of which uses a restricted subset of fatty acyl CoAs for N-acylation. Sphingolipids are found at high levels in nervous tissue, where they perform a variety of important functions in both the adult and the maturing brain. We now review what is known about the role of the acyl chain composition of ceramides and sphingolipids in normal brain development and in neurological diseases. Specifically, we attempt to integrate the information that is available about CerS expression and activity in the brain with the changes in the acyl chain composition of ceramide and complex sphingolipids in a number of neurodegenerative diseases and conditions, such as metachromatic leukodystrophy, neuronal ceroid lipofuscinoses, HIV infection, aging, Alzheimer's disease, ischemia, and epilepsy. We conclude that understanding the direct relationship between the CerS proteins and neurological conditions will be of great importance for delineating the precise roles of sphingolipids in the brain and is likely to be the subject of intense research activity in the years ahead. Ceramide forms the backbone of all complex sphingolipids and has been the focus of considerable attention in the past few years due to the discovery that ceramide plays vital roles as an intracellular messenger. Ceramide, which consists of a sphingoid long chain base to which a fatty acid is N-acylated, is synthesized in mammals by a family of ceramide synthases (CerS), each of which uses a restricted subset of fatty acyl CoAs for N-acylation. Sphingolipids are found at high levels in nervous tissue, where they perform a variety of important functions in both the adult and the maturing brain. We now review what is known about the role of the acyl chain composition of ceramides and sphingolipids in normal brain development and in neurological diseases. Specifically, we attempt to integrate the information that is available about CerS expression and activity in the brain with the changes in the acyl chain composition of ceramide and complex sphingolipids in a number of neurodegenerative diseases and conditions, such as metachromatic leukodystrophy, neuronal ceroid lipofuscinoses, HIV infection, aging, Alzheimer's disease, ischemia, and epilepsy. We conclude that understanding the direct relationship between the CerS proteins and neurological conditions will be of great importance for delineating the precise roles of sphingolipids in the brain and is likely to be the subject of intense research activity in the years ahead. Issue Title: Special Issue: Sphingolipids in Neurodegeneration Ceramide forms the backbone of all complex sphingolipids and has been the focus of considerable attention in the past few years due to the discovery that ceramide plays vital roles as an intracellular messenger. Ceramide, which consists of a sphingoid long chain base to which a fatty acid is N-acylated, is synthesized in mammals by a family of ceramide synthases (CerS), each of which uses a restricted subset of fatty acyl CoAs for N-acylation. Sphingolipids are found at high levels in nervous tissue, where they perform a variety of important functions in both the adult and the maturing brain. We now review what is known about the role of the acyl chain composition of ceramides and sphingolipids in normal brain development and in neurological diseases. Specifically, we attempt to integrate the information that is available about CerS expression and activity in the brain with the changes in the acyl chain composition of ceramide and complex sphingolipids in a number of neurodegenerative diseases and conditions, such as metachromatic leukodystrophy, neuronal ceroid lipofuscinoses, HIV infection, aging, Alzheimer's disease, ischemia, and epilepsy. We conclude that understanding the direct relationship between the CerS proteins and neurological conditions will be of great importance for delineating the precise roles of sphingolipids in the brain and is likely to be the subject of intense research activity in the years ahead.[PUBLICATION ABSTRACT] Ceramide forms the backbone of all complex sphingolipids and has been the focus of considerable attention in the past few years due to the discovery that ceramide plays vital roles as an intracellular messenger. Ceramide, which consists of a sphingoid long chain base to which a fatty acid is N -acylated, is synthesized in mammals by a family of ceramide synthases (CerS), each of which uses a restricted subset of fatty acyl CoAs for N -acylation. Sphingolipids are found at high levels in nervous tissue, where they perform a variety of important functions in both the adult and the maturing brain. We now review what is known about the role of the acyl chain composition of ceramides and sphingolipids in normal brain development and in neurological diseases. Specifically, we attempt to integrate the information that is available about CerS expression and activity in the brain with the changes in the acyl chain composition of ceramide and complex sphingolipids in a number of neurodegenerative diseases and conditions, such as metachromatic leukodystrophy, neuronal ceroid lipofuscinoses, HIV infection, aging, Alzheimer’s disease, ischemia, and epilepsy. We conclude that understanding the direct relationship between the CerS proteins and neurological conditions will be of great importance for delineating the precise roles of sphingolipids in the brain and is likely to be the subject of intense research activity in the years ahead.
Author	Futerman, Anthony H. Ben-David, Oshrit
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Snippet	Ceramide forms the backbone of all complex sphingolipids and has been the focus of considerable attention in the past few years due to the discovery that... Issue Title: Special Issue: Sphingolipids in Neurodegeneration Ceramide forms the backbone of all complex sphingolipids and has been the focus of considerable...
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SubjectTerms	Aging - metabolism Animals Biomedical and Life Sciences Biomedicine Brain - enzymology Brain Diseases - enzymology Ceramides - biosynthesis Ceramides - chemistry HIV Infections - enzymology Human immunodeficiency virus Humans Internal Medicine Mice Nerve Degeneration - enzymology Neurodegenerative Diseases - enzymology Neurology Neurosciences Review Paper Sphingosine N-Acyltransferase - genetics Sphingosine N-Acyltransferase - metabolism
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Title	The Role of the Ceramide Acyl Chain Length in Neurodegeneration: Involvement of Ceramide Synthases
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